Genetic Data Reveals an Easter Egg in Experimental Drugs

An entire class of experimental drugs, which were meant to treat immune system disorders, have an unexpected bonus feature: they are excellent painkillers.

In a paper that is jam-packed with surprises, Osamu Irie and Marzia Malcangio, researchers at Novartis, explained that gumming up an enzyme called Cathepsin S has been regarded as a surefire way to calm hyperactive parts of the immune system. But an astute observation led them to believe that plugging the biological molecule with an inhibitor could have other benefits as well.

While doing some genetics work, they noticed that injured rats with nerve damage produce a ton of the protein in their spinal columns, and wondered if a drug that could block it would prevent pain. They did some quick tests, and learned that a chemical, called LVHS, could shut down the enzyme and act as an analgesic in animals, but it is not fit to become a medication.

Their report, which appeared on the Journal of Medicinal Chemistry website last week, describes two chemicals with impressive stats. They can be taken orally, remain in the body long enough to be effective, and don’t seem to be toxic.

Early on in their study, Irie and Malcangio realized that the experimental drugs would not work on mutant forms of the enzyme. So when it came time to test them on animals, they hand picked lab rats without the mutation — an elegant example of personalized medicine — for critters!

The scientists did not suggest that their favorite chemicals will be tested on humans, but they did indicate that both will be useful tools to answer a burning question: How do substances that fiddle with Cathepsin S block pain signals?